The effects of polyphenol-rich pomegranate extract on the microbial conversion of L-carnitine into the proatherogenic trimethylamine (360G-Wellcome-226902_Z_23_Z)

L-carnitine is an essential nutrient, mainly found in red meat. Gut microbiota metabolise L-carnitine to trimethylamine (TMA), which is then converted in the liver to a harmful compound called trimethylamine N-oxide (TMAO). Strong epidemiological evidence links TMAO with atherosclerosis and various cardiometabolic diseases. However, suggested treatments to reduce TMAO, such as broad-spectrum antibiotics, have adverse effects. I aim to understand the effects of pomegranate extract to inhibit the microbial conversion of l-carnitine to TMA (and, subsequently, TMAO). Pomegranate is naturally high in dietary polyphenols, which are thought to reduce inflammation and oxidative stress. Using a colon model, I will investigate the effects of individual pomegranate polyphenols on microbial L-carnitine metabolism. Additionally, I will use metagenomics to study the microbial genes present in the gut, which helps to identify whether treatment with pomegranate extract changes the function and composition of the gut microbiome. Finally, I will conduct a human trial to evaluate whether the inhibition of L-carnitine metabolism by pomegranate polyphenols is also observed in vivo in humans. This research will contribute to the evidence for a diet or supplement that may help to reduce TMA and TMAO levels, which can subsequently reduce the risk of cardiometabolic diseases among populations worldwide.